IL-4 and IL-10 inhibition of spontaneous monocyte apoptosis is associated with Flip upregulation.

Human peripheral blood monocytes undergo spontaneous apoptosis in culture. Spontaneous monocyte apoptosis is regulated by the death ligand, Fas Ligand (FasL) binding to its receptor Fas. The pro-inflammatory molecules, LPS and IL-1beta, prevent spontaneous monocyte apoptosis. Here, we demonstrate that the anti-inflammatory cytokines IL-4 and IL-10 inhibit spontaneous monocyte apoptosis compared to control-treated cells. IL-4- or IL-10-mediated suppression of spontaneous monocyte apoptosis is associated with the induction of Flip, an essential inhibitor of the Fas-death signal. In contrast, IL-4 and IL-10 inhibit LPS or IL-1beta induced pro-inflammatory cytokine production. These data suggest that in monocytes IL-4 or IL-10 has a dual function, to inhibit pro-inflammatory cytokine production and to suppress spontaneous apoptosis.